Colorectal cancer genomics with primary and metastatic samples
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ABSTRACT:
PROVIDER: EGAS00001006465 | EGA |
REPOSITORIES: EGA
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Project description:We performed RNAseq analysis of metastatic colorectal cancer from 16 patients. Normal adjacent tissue, primary tissue, and metastatic tissue were analyzed to uncover metastatic progression and difference between primary and distant metastatic lesions.
| EGAS00001006464 | EGA
Project description:Copy number analyses of regionally separated biopsies from primary and metastatic lesions of five colorectal cancers A total of 35 intratumoral biopsies were obtained from primary and metastatic lesions of five colorectal cancers. Board-certified pathologists reviewed the hematoxylin&eosin stained sections and identified tumor-rich regions (> 80% purity) to ensure minimal contamination of normal tissues. We selected two to six different areas for biopsy that were at least 5mm apart in primary and distant metastatic lesions from a same patient. Copy number profiling was performed using Agilent 180K platform according to the manufacturer's protocol. The genomic DNA obtained from the adjacent normal tissues were used as reference genomic DNA for the tumor DNA of the corresponding patients.
2014-06-16 | E-GEOD-58512 | biostudies-arrayexpress
Project description:We present a novel approach for investigating transcriptomic differences between primary colorectal cancers (CRC) and distant CRC metastases, which may help to identify primaries at high risk for future dissemination and to inform the development of metastasis-targeted therapies. Eliminating tissue specificity of the “host” organs where tumors are located and adjusting for confounders such as exposure to chemotherapy and radiation, allows for an effective comparison of primary CRC and metastatic lesion transcriptomes at both the gene and pathway levels. Using this approach, our discovery-validation design identified that metastases are characterized by reduced epithelial-mesenchymal-transition (EMT) but increased MYC target and DNA repair pathway activities. The most significant gene-level expression differences between primaries and metastases were in FBN2 and MMP3, which showed over a 7-fold difference. In addition, we uncovered two distinct subtypes of CRC metastases that are characterized by either EMT-inflammatory or proliferative phenotypes, and demonstrated that none of the metastases examined were of consensus molecular subtype (CMS) 3 suggesting subtype exclusivity. Highlighting transcriptome differences between primary tumors and CRC metastases delineates pathways that may be activated in metastases and may assist in the development and/or selection of existing targeted treatment regimens for individuals with metastatic disease.
2019-05-18 | GSE131418 | GEO
Project description:<p>Molecular profiling for somatic mutations that predict response to anti-EGFR therapy in colorectal cancer (CRC) has become standard practice. However, abundant tissue from metastatic lesions is not always available from patients with metastatic CRC. Concerns involving genetic heterogeneity between primary and metastatic lesions have called into question the suitability of profiling primary tumors in patients with metastatic disease. Further, the identification of discordant mutations between matched primary and metastatic tumors would be of biological interest for the delineation of biomarkers of tumor progression and metastasis.</p> <p>To explore the degree of genetic heterogeneity between matched primary and metastatic tumors in CRC, we performed whole genome sequencing of four patient "trios" comprised of a primary colon tumor, a liver metastasis, and matched normal (non-cancerous) tissue. Somatic mutations and indels were called in each tumor and compared between primary and metastatic lesions.</p>
| phs000790 | dbGaP
Project description:Genomic profiling of primary colorectal carcinomas was performed in relation to the spread of CTCs in peripheral and hepatic venous blood, liver metastases, and distant metastases beyond the liver, with the intent to identify specific patterns for the different stages of metastatic spread.
2018-08-21 | GSE82228 | GEO
Project description:Distant metastasis is the major causes of death in colorectal cancer (CRC) patients. In order to identify genes influencing the prognosis of patients with CRC, we compared gene expression in primary tumors with and without distant metastasis using an oligonucleotide microarray. We also examined the expression of the candidate gene in 100 CRC patients by quantitative real-time reverse transcription PCR and studied the relationship between its expression and the prognosis of patients with CRC. As a result, we identified MUC12 as a candidate gene involved in metastasis processes by microarray analysis. Quantitative real-time reverse transcription PCR showed that MUC12 expression was significantly lower in cancer tissues than in adjacent normal tissues (P < 0.001). In stage II and stage III CRC, patients with low expression showed worse disease-free survival (P = 0.038). Multivariate analysis disclosed that MUC12 expression status was an independent prognostic factor in stage II and stage III CRC (relative risk, 9.532; 95% confidence interval, 2.303-41.905; P = 0.002). This study revealed the prognostic value of MUC12 expression in CRC patients. Moreover, our result suggests MUC12 expression is a possible candidate gene for assessing postoperative adjuvant therapy for CRC patients. Total of 111 microarray datasets (77 for LCM samples, and 17 pairs for homogenized samples from tumor and adjacent tissues) were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software together with BioConductor package, as described previously. Then, the gene expression levels were log2-transformed, and 62 control probe sets were removed for further analysis. In order to identify a set of genes associated with development of metastatic recurrence, we performed Wilcoxon rank-sum test for gene expression differences of 54,613 probe sets between recurrence and non-recurrence groups. Similarly, Wilcoxon singed-rank test was conducted to select genes which showed significant expression difference between tumor and adjacent tissue. Then, we selected a set of genes that satisfied both of above two criteria.
2010-03-05 | E-GEOD-18105 | biostudies-arrayexpress
Project description:Background: Liver metastasis is the major cause of death following a diagnosis of colorectal cancer (CRC) and is a major health burden. Most molecular studies of CRC have profiled primary tumor samples and not the metastasis samples. In this study, we compared the copy number profiles of matched primary and liver metastatic CRC to better understand how the genomic structure of primary CRC differs from the metastasis. This has important implications for whether it is justified to base therapeutic approaches solely on data from the primary tumour. Methods: Paired primary and metastatic tumours from 16 patients and their adjacent normal tissue samples were analyzed using Single-Nucleotide-Polymorphism (SNP) arrays to determine copy number alterations. Nine patients had a synchronous liver metastasis at the time of CRC diagnosis and 7 patients developed a liver metastasis metachronously. Genome-wide chromosomal copy number alterations were assessed, with particular attention to 189 genes known to be somatically altered in CRC and 25 genes that are clinically actionable in CRC. These data were analyzed with respect to the timing of primary and metastatic tissue resection and with exposure to chemotherapy. Results: The genomic divergence with the whole genome duplication correction applied the average percent copy number discordance across all pairs of samples was 22.02%. The pairs of tumour samples collected prior to treatment revealed a significantly higher copy number differences compared to previously treated liver metastasis samples (P=0.024). However, loss of heterozygosity (LOH) acquired in metastasis was significantly higher in previously treated liver metastasis samples compared to treatment naïve liver metastasis samples (P= 0.0064) and which included where KRAS mutation was present in the primary cancers but was not detectable in the metastatic sample following chemotherapy. With regard to 25 genes that are clinically actionable in CRC, amplification of the genes ERBB2, FGFR1, CDK8 or PIK3CA was observed in the metastatic tissue of 4 patients but not in the matched primary CRC. In these cases, knowledge of these metastatic specific alterations could have informed therapeutic decision making and may have improved patient outcome. Conclusion: Intra-patient genomic discrepancies observed between primary and metastatic tissue
2018-02-14 | GSE100787 | GEO
Project description:a considerable portion of patients with early T stage who were supposed to have a low distant metastatic probability, were diagnosed with metastatic cancer. Our study aims to evaluate characteristics of T1M1patients via cDNA microarray.
2020-07-06 | GSE146480 | GEO
Project description:Metastasis of breast cancer to other distant organs is fatal to patients. However, few studies have revealed biomarkers associated with distant metastatic breast cancer. Furthermore, the inability of current biomarkers such as HER2, ER and PR, in accurately differentiating between distant metastatic breast cancers from non-distant metastatic ones necessitates the development of novel biomarkers. An integrated proteomics approach that combines filter-aided sample preparation, tandem mass tag labeling (TMT), high pH fractionation, and high resolution MS was applied to acquire in-depth proteome data of distant metastatic breast cancer FFPE tissue. Bioinformatics analyses for gene ontology and signaling pathways using differentially expressed proteins (DEPs) were performed to investigate molecular characteristics of distant metastatic breast cancer. In addition, real-time polymerase chain reaction (RT-PCR) and invasion/migration assays were performed to validate the differential regulation and functional capability of biomarker candidates. A total of 9,459 and 8,760 proteins were identified from the pooled sample set and the individual sample set, respectively. Through our stringent criteria, TUBB2A was selected as a novel biomarker. The metastatic functions of the candidate were subsequently validated. Bioinformatics analysis using DEPs were able to characterize the overall molecular features of distant metastasis as well as investigate the differences across breast cancer subtypes. Our study is the first to explore the distant metastatic breast cancer proteome using FFPE tissue. The depth of our dataset enabled the discovery of novel biomarker and the investigation of proteomic characteristics of distant metastatic breast cancer. The distinct molecular features of breast cancer subtypes were also observed. Our proteomic data has important utility as a valuable resource for the research on distant metastatic breast cancer.
2020-06-05 | PXD016061 | Pride
Project description:Profiling of genetically matched normal adjacent tissue, primary tumor and metastatic lymph-node to identify cancer and metastasis genes.
2006-11-21 | E-MEXP-44 | biostudies-arrayexpress